Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release

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Titel: Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release
Autoren: Zhou, Xuehan, Stine, Carrie, Prada, Patricia Oliveira, Fusca, Debora, Assoumou, Kevin, Dernic, Jan, Bhat, Musadiq A, Achanta, Ananya S, Johnson, Joseph C, Pasqualini, Amanda Loren, Jadhav, Sanjana, Bauder, Corinna A, Steuernagel, Lukas, Ravotto, Luca, Benke, Dietmar, Weber, Bruno, Suko, Azra, Palmiter, Richard D, Stoeber, Miriam, Kloppenburg, Peter, Brüning, Jens C, Bruchas, Michael R, Patriarchi, Tommaso
Weitere Verfasser: University of Zurich, Bruchas, Michael R, Patriarchi, Tommaso
Quelle: bioRxiv
Nat Commun
Nature Communications, Vol 15, Iss 1, Pp 1-20 (2024)
Nature Communications, 15 (1)
Nature Communications
Publication Status: Preprint
Verlagsinformationen: Springer Science and Business Media LLC, 2023.
Publikationsjahr: 2023
Schlagwörter: Receptors, Opioid / metabolism, Male, Receptors, Opioid / genetics, Science, 10050 Institute of Pharmacology and Toxicology, 610 Medicine & health, 1600 General Chemistry, Biosensing Techniques, Ligands, Article, Nociceptin Receptor, Ventral Tegmental Area / metabolism, Mice, 1300 General Biochemistry, Genetics and Molecular Biology, Biosensing Techniques / methods, Animals, Humans, Opioid Peptides / metabolism, Neurons, Nociceptin, Neurons / metabolism, Ventral Tegmental Area, Brain, 3100 General Physics and Astronomy, Mice, Inbred C57BL, HEK293 Cells, Opioid Peptides, Receptors, Opioid, 570 Life sciences, biology, Brain / metabolism
Beschreibung: Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including motivation, stress, feeding, and sleep. The functional relevance of N/OFQ action in the mammalian brain remains unclear due to a lack of high-resolution approaches to detect this neuropeptide with appropriate spatial and temporal resolution. Here we develop and characterize NOPLight, a genetically encoded sensor that sensitively reports changes in endogenous N/OFQ release. We characterized the affinity, pharmacological profile, spectral properties, kinetics, ligand selectivity, and potential interaction with intracellular signal transducers of NOPLight in vitro. Its functionality was established in acute brain slices by exogeneous N/OFQ application and chemogenetic induction of endogenous N/OFQ release from PNOC neurons. In vivo studies with fibre photometry enabled direct recording of NOPLight binding to exogenous N/OFQ receptor ligands, as well as detection of endogenous N/OFQ release within the paranigral ventral tegmental area (pnVTA) during natural behaviors and chemogenetic activation of PNOC neurons. In summary, we show here that NOPLight can be used to detect N/OFQ opioid peptide signal dynamics in tissue and freely behaving animals.
Publikationsart: Article
Other literature type
Dateibeschreibung: application/pdf; application/application/pdf; ZORA_s41467_024_49712_0.pdf - application/pdf
Sprache: English
ISSN: 2041-1723
DOI: 10.1038/s41467-024-49712-0
DOI: 10.1101/2023.05.26.542102
DOI: 10.5167/uzh-261093
DOI: 10.3929/ethz-b-000680781
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/38918403
https://pubmed.ncbi.nlm.nih.gov/37292957
https://doaj.org/article/85f93020cae0443ca2de0481924bf37c
http://hdl.handle.net/20.500.11850/680781
Rights: CC BY
URL: http://creativecommons.org/licenses/by-nd/4.0/This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, and only so long as attribution is given to the creator. The license allows for commercial use.
Dokumentencode: edsair.doi.dedup.....90e2c8ec895fdbf0b6b240626d49745f
Datenbank: OpenAIRE
Beschreibung
Abstract:Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including motivation, stress, feeding, and sleep. The functional relevance of N/OFQ action in the mammalian brain remains unclear due to a lack of high-resolution approaches to detect this neuropeptide with appropriate spatial and temporal resolution. Here we develop and characterize NOPLight, a genetically encoded sensor that sensitively reports changes in endogenous N/OFQ release. We characterized the affinity, pharmacological profile, spectral properties, kinetics, ligand selectivity, and potential interaction with intracellular signal transducers of NOPLight in vitro. Its functionality was established in acute brain slices by exogeneous N/OFQ application and chemogenetic induction of endogenous N/OFQ release from PNOC neurons. In vivo studies with fibre photometry enabled direct recording of NOPLight binding to exogenous N/OFQ receptor ligands, as well as detection of endogenous N/OFQ release within the paranigral ventral tegmental area (pnVTA) during natural behaviors and chemogenetic activation of PNOC neurons. In summary, we show here that NOPLight can be used to detect N/OFQ opioid peptide signal dynamics in tissue and freely behaving animals.
ISSN:20411723
DOI:10.1038/s41467-024-49712-0